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RESEARCH PRODUCT

Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients With Coronary Artery Disease

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Along with superoxide dismutase, glutathione peroxidase 1 is one of the cellular antioxidant enzymes that have a key role in controlling reactive oxygen species. It uses glutathione to reduce hydrogen peroxide to water and lipid peroxides to their respective alcohols. There are suggestions from in vitro and animal studies that these enzymes could protect against atherosclerosis. This prospective study examined the possibility that relatively high activity of antioxidant enzymes protects against cardiovascular events. The study population included 636 patients suspected of having coronary artery disease who were followed for a median period of 4.7 years. Stable angina was present in 510 patients and symptoms of unstable angina in 133. Coronary angiography disclosed coronary artery disease with more than 30% stenosis of at least 1 major coronary artery in 558 patients. Enzyme activities were measured in washed red blood cells. Baseline levels of glutathione peroxidase 1 activity were significantly lower in patients who died of cardiac causes or had a nonfatal myocardial infarction than in those not having either of these events. The relationship persisted when patients who died and those with nonfatal events were separately analyzed. Rates of cardiovascular events increased across decreasing quartiles of baseline enzyme activity; patients in the lowest quartile had approximately 3 times more events than those in the highest quartile. Enzyme activity was lower in current smokers than in those who had never smoked. Except for statins, which were associated with higher glutathione peroxidase 1 activity, there was no apparent association between cardiovascular medications and the activity of either glutathione peroxidase 1 or superoxide dismutase. The inverse relationship between glutathione peroxidase 1 activity and the relative risk of coronary disease events was changed very little after adjusting for cardiovascular risk factors and clinical features. Patients with the highest glutathione peroxidase 1 activity had a hazard ratio of 0.29 (95% confidence interval, 0.14-0.60) compared with those in the lowest quartile. These findings indicate that in patients with coronary artery disease, red blood cell levels of glutathione peroxidase 1 activity are inversely associated with the risk of future cardiovascular events, both fatal and nonfatal. Estimating enzyme activity might prove helpful for identifying patients who would benefit from prophylactic antioxidant treatment.